692 ENDOCRINE PRACTICE Vol 20 No. 7 July 2014

AACE/ACE Guidelines

Jeffrey I. Mechanick, MD, FACP, FACE, FACN1; Pauline M. Camacho, MD, FACE2;Alan J. Garber, MD, PhD, FACE3; Jeffrey R. Garber, MD, FACP, FACE4;

Rachel Pessah-Pollack, MD, FACE5; Steven M. Petak, MD, JD, MACE6; Vin Tangpricha, MD, PhD, FACE7; Dace L. Trence, MD, FACE8

American Association of Clinical Endocrinologists and American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

Copyright © 2014 AACE.

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AACE GUIDELINES FOR GUIDELINES TASK FORCE

ChAIR

Jeffrey I. Mechanick, MD, FACP, FACE, FACN

PRIMARY WRITERS

Pauline M. Camacho, MD, FACEAlan J. Garber, MD, PhD, FACE

Jeffrey R. Garber, MD, FACP, FACERachel Pessah-Pollack, MD, FACESteven M. Petak, MD, JD, MACEVin Tangpricha, MD, PhD, FACE

Dace L. Trence, MD, FACE

SPECIAL REVIEWER

Mor Peleg, PhD

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ABSTRACT

In 2010, the American Association of Clinical Endocrinologists (AACE) published an update to the original 2004 guidelines. This update hybridized strict evidence-based medicine methods with subjective factors and improved the efficiency of clinical practice guidelines (CPG) production, clinical applicability, and usefulness. Current and persistent shortcomings involving suboptimal implementation and protracted development timelines are addressed in the current 2014 update. The major advances include 1) formulation of an organizational educational strategy, represented by the AACE Council on Education, to address relevant teaching and decision-making tools for clinical endocrinologists, and to generate specific clinical questions to drive CPG, clinical algorithm (CA), and clini-cal checklist (CC) development; 2) creation and prioritiza-tion of printed and online CAs and CCs with a supporting evidence base; 3) focus on clinically relevant and ques-tion-oriented topics; 4) utilization of “cascades,” where there can be more than 1 recommendation for 1 clinical question; and 5) incorporation of performance metrics to validate, optimize, and effectively update CPG, CAs, and CCs. Efforts continue to translate these clinical tools to electronic formats that can be integrated into a paperless healthcare delivery system, as well as applying them to diverse clinical settings by incorporating transcultural fac-tors. (Endocr Pract. 2014;20:000-000)

Abbreviations:AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; CA = clinical algorithm; CC = clini-cal checklist; CPG = clinical practice guidelines; GAC = guidelines, algorithms, and checklists; EBM = evi-dence-based medicine; G4G = guidelines for guide-lines (G4G-2004, G4G-2010, G4G-2014); POEMS = patient-oriented evidence that matters; PRCT = pro-spective randomized controlled trial

INTRODUCTION

The development of “White Papers” − authoritative documents on a specific topic − is an educational priority for the American Association of Clinical Endocrinologists (AACE). These evidence-based activities strategically tar-get endocrine topics that are critical to clinical practice, utilized for healthcare policy, incorporated in formal post-graduate training, and represent areas infused with new and important information. The production of AACE clinical practice guidelines (CPG) was deemed necessary in this regard and resulted in many high-quality publications for nearly 2 decades. In 2004 (1), the AACE recognized that standardization of CPG production was required to opti-mize the process, and the first “guidelines for guidelines” (G4G) were published. Shortcomings of the 2004 G4G (G4G-2004) were identified, prompting an update in 2010 (G4G-2010) (2). The reader is referred to these previous G4G for further detail. The iterative process of AACE CPG optimization is given in Table 1. A list of AACE CPG pub-lished after 2009, adhering with G4G-2010, is provided in Table 2. There are 2 broad drivers for AACE’s critical assess-ment of white paper development strategies. The first driver relates to the consistent requirement for diligence regard-ing methodology, utilization, applicability, relevance, per-formance, and other validation metrics. For instance, the primacy of prospective, randomized controlled studies, to the exclusion of the total weight of evidence, to guide public health policy (3), or the general acceptance of meta-analyses as high-level evidence despite significant pitfalls (4), have raised considerable doubt in the value of CPG evidence rating systems. The second driver is to keep pace with accelerated discovery, tight publication timelines, and paradigm changes in healthcare, such as complex decision-making, electronic health records, informatics, molecular and systems biology, self-learning technologies, and glo-balization with transcultural imperatives (5-7). Alonso-Coello et al (8) found that CPG quality has remained at moderate-to-low levels over the past 2 decades, primarily due to problems with stakeholder involvement and editorial independence. Bancos et al (5) conducted

From the 1Clinical Professor of Medicine, Director, Metabolic Support, Division of Endocrinology, Diabetes, and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York; 2Professor of Medicine; Loyola University Medical Center, Director, Loyola University Osteoporosis and Metabolic Bone Disease Center, Maywood, Illinois; 3Professor, Departments of Medicine, Biochemistry and Molecular Biology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; 4President, American College of Endocrinology, Chief, Endocrinology, Harvard Vanguard Medical Associates, Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts; 5Assistant Clinical Professor, Mount Sinai School of Medicine, New York, NY, ProHealth Care Associates, Division of Endocrinology, Lake Success, New York; 6Department of Medicine, Division of Endocrinology, Houston Methodist Hospital, Houston, Texas; 7Associate Professor of Medicine, Program Director, Endocrinology Fellowship, Division of Endocrinology, Diabetes & Lipids, Emory University School of Medicine, Atlanta, Georgia; 8Professor of Medicine, Division of Metabolism, Endocrinology and Nutrition, Director, Endocrine Fellowship Program Director, Diabetes Care Center University of Washington, Seattle, Washington.Address correspondence to American Association of Clinical Endocrinologists, 245 Riverside Ave, Suite 200, Jacksonville, FL 32202. E-mail: publications@aace.com. DOI:10.4158/EP14166.PSTo purchase reprints of this article, please visit: www.aace.com/reprints.Copyright © 2014 AACE.

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a systematic review of endocrine CPG published from 2007-2010 and identified 3 areas for focused improve-ment: sound methodology, stakeholder involvement, and implementation strategies. The findings were placed within the context of the GRADE system for CPG development, which was also the subject of an extensive 20-part series

of articles in the Journal of Clinical Epidemiology, begin-ning in 2011 (9). This systematic process of critical assess-ment, enriched with empirical validation, is commended and serves as a model for the AACE G4G program. Nevertheless, if rigorous and extensive derivative papers are constantly required − somewhat as an operating manual

Table 1Iterative process of G4G optimization

G4G Version Attributes Shortcomings

G4G-2004 Formal EBM Lengthy production timeline- evidence rating High production costs- recommendation grading Burdensome methodologyIncorporation of subjective factors Inexact evidence rating/recommendation gradingRecommendation cascades Inexact codification of subjective factors/qualifiersTransparency Inexact review processMultiplicity of interest disclosures May lack patient-oriented relevanceNo industry involvement with development Dependence on PRCT for question framing and recommendation grading

G4G-2010 Shorter development timeline (<1 year) Difficult to implementMandate constrained to clinical question(s) No electronic implementationMiddle-range literature searching Not linked to reader surveysUsing patient-oriented evidence that matters No performance metricsFormal 4-step EBM No validation studies- evidence rating

- numerical descriptors- semantic descriptors

- modify with subjective factors- recommendation grading- append recommendation qualifiersFormal multilevel review process

G4G-2014 Formalized protocol for instrument selection- CPG- CA- CCActualize and optimize electronic implementationFormalize performance metrics and validation studies

CA = clinical algorithm; CC = clinical checklist; CPG = clinical practice guidelines; EBM = evidence-based methodology;G4G = guidelines for guidelines; PRCT = prospective randomized controlled trial.

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− in order for CPGs to be used properly, then how practical could CPGs really be? Easy-to-use visually and graphically oriented instru-ments, such as clinical algorithms (CAs) and clinical check-lists (CCs) should be used to replace underutilized, heavily texted CPGs. By employing these instruments, CPGs will then become more relevant, easier to implement, and easier to incorporate into electronic health record decision-mak-ing and order sets (10). CAs contain an initial state, input variables, well-defined successive states, and step-by-step graphically displayed transitions corresponding to reasoning decisions. A popular algorithm expression is the flowchart where different opera-tions are represented by node shape (e.g., “sequence,” “go to,” and “if-then-else”). This formalized set of rules can

manage complex medical problems but do not quantitate probabilities or outcome values as found in a decision analy-sis (11). Hence, CAs perform better when there is increased empiric certainty or levels of scientific substantiation with each decision; decision analyses are more appropriate in problem solving where uncertainties predominate (11). A list of CA attributes is provided in Table 3. Various endocrine CA have been constructed with the majority implemented and validated (Table 4). Nevertheless, the routine use of CA in endocrinology is lacking. CCs for physicians are primarily patient safety tools and have been validated in medical settings (23,24). Various formats exist for CCs, ranging from laundry lists for equip-ment, to sequential and iterative lists for procedures, to “criteria of merit” lists for focused evaluations (25). These

Table 2American Association of Clinical Endocrinologists (AACE) Clinical Practice Guidelines Published After 2009

Year Title Reference

2010 American Association of Clinical Endocrinologists, Associazione Medici Endo Pract. 2010;16(Suppl 1):1-43 Endocrinologi, and European Thyroid Association Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules

2010 American Association of Clinical Endocrinologists Guidelines for Clinical Endo Pract. 2010;16(Suppl 3):1-37 Practice for the Diagnosis and Treatment of Postmenopausal Osteoporosis

2011 American Association of Clinical Endocrinologists Medical Guidelines Endo Pract. 2011;17(Suppl 2):1-53 For Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan

2011 Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Endo Pract. 2011;17:e1-e65 Guidelines of the American Thyroid Association and American Association Of Clinical Endocrinologists

2011 American Association of Clinical Endocrinologists Medical Guidelines Endo Pract. 2011;17(Suppl 4)1-44 for Clinical Practice for the Diagnosis and Treatment of Acromegaly – 2011 Update

2011 American Association of Clinical Endocrinologists Medical Guidelines Endo Pract. 2011;17(Suppl 6):1-25 for Clinical Practice for the Diagnosis and Treatment of Menopause

2012 American Association of Clinical Endocrinologists’ Guidelines for Endo Pract. 2012;18(Suppl 1):1-78 Management of Dyslipidemia and Prevention of Atherosclerosis

2012 Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored Endo Pract. 2012;18:988-1028 by the American Association of Clinical Endocrinologists and the American Thyroid Association

2013 Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, Endo Pract. 2013;19:1-36 and Nonsurgical Support of the Bariatric Surgery Patient – 2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery

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practice tools address performance gaps and human errors of omission, especially in high stress and complex care set-tings. Performance gaps include human fallibility, incompe-tence, impairment, and inability to effectively communicate (26). A checklist can provide a standardized, evidence-based tool to improve clinical practice, outcomes, and costs, as exemplified in preventive care (27) and type 2 diabetes care environments (28). Checklists also fill a niche by pro-viding greater clarity than prosaic CPG and are simpler to execute than CAs (Fig. 1). Factors that influence success-ful CC implementation are given in Table 5. Despite these

arguments, the widespread use of CCs has been hampered by a lack of standardization and familiarity (25). The AACE has already published CAs and related graphics, such as roadmaps, as well as CCs (Table 6). The 2014-2016 AACE Strategic Plan warrants further development of practical AACE CAs and CCs. This 2014 G4G update (G4G-2014) will apply to pure CPG, which remain indispensable, CAs, which will include abbreviated appended supporting text, and CCs, which can be written as stand-alone documents or part of a larger CPG or CA. Additionally, this G4G-2014 will further detail the use of

Table 3List of Attributes of Clinical Algorithmsa

history Development Features Computer science Identify complex problem Graphical clarity > Prose clarity Artificial intelligence Identify specific questions Concise stepwise decisions Medical decision-making Identify performance requirement - Clinical state Electronic health records Identify target audience - Diagnostic decision

Utilize, validate, modify - Therapeutic decision - Complexity managed by process - Same diligence as CPG development

- Less granular Annotations and footnotes Case examples

Expert review Consistency and correctness assured

CPG = clinical practice guidelines a See reference 7

Table 4Clinical Algorithms in Endocrinologya

Description Validation (Y/N)b Reference

Acute bacterial suppurative thyroiditis N 12 Artificial endocrine pancreas glycemic control Y 13,14 Chronic testicular pain N 15 Framingham cardiovascular disease Y 16 Hypocalcemia after thyroidectomy, based on PTH and calcium Y 17,18 Laparoscopic adrenalectomy approach Y 19 Osteoporotic fracture risk estimation Y 20 Ovarian hyperstimulation syndrome – composite scoring system Y 21 Ovarian hyperstimulation syndrome – poststimulation follicle count N 22

PTH = parathyroid hormone a excluding AACE algorithms provided in table 6 b evidence presented to support use of algorithm

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electronic implementation, cascades, and transculturaliza-tion to better assimilate personalized medicine advances in a global arena.

Protocol Updates The mandate for an AACE CPG, CA, or CC will con-tinue to originate from the AACE President, Executive Committee, and/or Publications Committee, consistent with the 2014-2016 AACE/ACE Plan, and will require AACE Board of Directors approval. Once document pro-duction is approved, a Task Force Chair will be assigned and a writing group selected. The timelines from mandate to journal submission will be limited to 6 to 12 months depending on the topic scope and need. All AACE CPG,

CAs, and CCs will have a date stamp and be amenable for electronic implementation (30). Piloting, validation, and iterative optimization processes will need to be devised and implemented for all future AACE CPG, CAs, or CCs. Content validation can take the form of surveys, and clini-cal validation can take the form of more elaborate retro-spective or prospective interventional studies. The AACE will also plan formal educational programs based on new and revised CPG, CAs, and CCs.

G4G-2014: CPG Specific indications for mandate. Pure CPG must be relevant to clinical endocrine practice and may be consid-ered when 1) a new clinical endocrine problem has arisen or

Fig. 1. Features of guidelines, algorithms, and checklists.

Table 5Factors Influencing the Implementation of Clinical Checklistsa

Positive Negative

Developing local champions Anxiety and resistance due to unfamiliarity Developing and demonstrating organizational leadership Personnel hierarchies Creating a culture that prioritizes patient safety Logistics and time consumption Accountability Process duplication Validation with appropriate metrics, monitoring, and recording Relevance with clinical practice scenarios Education, training, and periodic audits with feedback Overused or underused in certain settings Create an evidence base

a See reference 29

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2) new information and therapies for an established clinical endocrine problem are sufficient to either develop a new document or update a previous document. New informa-tion and therapies include novel diabetes technologies and oncological molecular markers, where seminal changes in an evidence base would relate to new interventions, such as bariatric procedures, or new clinical trial data, such as screening for hypothyroidism in pregnancy. Attributes. Pure CPG must incorporate the following attributes during the development process:

• 4-step evidence-based medicine (EBM) method-ology (Fig. 2),

• Multilevel review process,• Option to publish a “core” set of recommendations, • Option to append international modules that are

cosponsored with local professional medical organizations, and

• Expiration date after 3 years, at which time updat-ing is considered

In addition, CPG must incorporate attributes that address persistent problems and criticisms that have lim-ited their implementation. These new attributes include a more efficient timeline to be less than 6 to 12 months, allowing for the incorporation of more timely content. Supporting text will begin with a brief introduction describing the need for changes in the new CPG without relying upon reference citation alone. Furthermore, the CPG will be divided in to an Executive Summary that is expeditiously available online and also published in print, with a detailed appended evidence base available online without pagination restrictions. This protocol allows cost-containment with print pagination and simultaneously avoids unnecessary content restrictions on supporting evi-dence and explanatory text. AACE CPG may also provide cascades for each rec-ommendation. Cascades provide for options for a given

clinical question and challenge the antiquated paradigm of “1 question – 1 recommendation.” This feature has not been optimally utilized, but in a global arena of clinical endocrinology, an expanded epigenomic evidence base, and personalized medicine, the AACE will need to address individualities in many different clinical settings and cul-tures, as well as variations in clinical settings that may result from differences in available resources, economic constraints, levels of physician training, and patients’ ability to adhere with recommendations. These variations overlap with categorical transcultural factors (e.g., geog-raphy, race and ethnicity, epigenomics, social, political, policy, economic, religious, and attitudinal) (31). The glo-balization of medicine, and clinical endocrinology in par-ticular, especially with many international AACE chapters and initiatives, lends urgency to the incorporation of trans-cultural approaches to patient care within white papers.

G4G-2014: CAs Specific indications for mandate. CAs must be rele-vant to clinical endocrine practice and should be consid-ered whenever new information is available that signifi-cantly changes clinical endocrine practice. Attributes. CAs will incorporate the following attributes:

• Comprehensive in nature for a given topic,• Based where possible on strong recommendations

(Grade A or B), • Weaker recommendations (Grade C) and expert

opinion (Grade D) to be incorporated after exten-sive vetting and full consensus of primary authors,

• Intuitive process flow that reflects contemporary clinical endocrine practice,

• Provision of management options with explana-tions in appended text,

• Simple and detail balanced to provide essential information while allowing for clinical judgment,

Table 6 AACE Clinical Algorithms, Roadmaps, and Checklists

Year Title Reference

2007 Road Maps to Achieve Glycemic Control in Type 2 Diabetes Mellitus Endo Pract. 2007;13:260-268 2009 Statement by an American Association of Clinical Endocrinologists/ Endo Pract. 2012; 15:540-559 American College of Endocrinology Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control 2013 Preoperative Checklist for Bariatric Surgery Endo Pract. 2013;19:1-36 2013 Postoperative Checklist for Bariatric Surgery Endo Pract. 2013;19:1-36 2013 AACE Comprehensive Diabetes Management Algorithm – 2013 Endo Pract. 2013;19:327-336

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Fig. 2. 4-Stage evidence-based medicine methodology.

2010 AACE Protocol for Production of Clinical Practice GuidelinesStep IV: Examples of Qualifiers That May Be Appended to Recommendations

Cost-effectiveness Risk-benefitanalysis Evidencegaps Alternativephysicianpreferences(dissentingopinions) Alternativerecommendations(“cascades”) Resourceavailability Culturalfactors Relevance(patient-orientedevidencethatmatters)

AdaptedfromMechanicketal.Endocr Pract.2010.16:270-283.

2010 AACE Protocol for Production of Clinical Practice GuidelinesStep III: Grading of Recommendations; How Different Evidence Levels

Can Be Mapped to the Same Recommendation Gradea

BELSubjective factor

impact Two-thirdsconsensus

Mapping Recommendation grade

1 None Yes Direct A

2 Positive Yes Adjustup A2 None Yes Direct B1 Negative Yes Adjust down B3 Positive Yes Adjustup B3 None Yes Direct C2 Negative Yes Adjust down C4 Positive Yes Adjustup C4 None Yes Direct D3 Negative Yes Adjust down D

1,2,3,4 NA No Adjust down D

Abbreviations:AACE=AmericanAssociationofClinicalEndocrinologists1=strongevidence;2=intermediateevidence;3=weakevidence;4=noevidence.aStartingwiththeleftcolumn,bestevidencelevels(BEL),subjectivefactors,andconsensusmaptorecommendationgradesintherightcolumn.Whensubjectivefactorshavelittleornoimpact(“none”),thentheBELisdirectlymappedtorecommendationgrades.Whensubjectivefactorshaveastrongimpact,thenrecommendationgradesmaybeadjustedup(“positive”impact)ordown(“negative”impact).Ifatwo-thirdsconsensuscannotbereached,thentherecommendationgradeisD.NA=notapplicable(regardlessofthepresenceorabsenceofstrongsubjectivefactors,theabsenceofatwo-thirdsconsensusmandatesarecommendationgradeD).AdaptedfromMechanicketal.Endocr Pract.2010.16:270-283.

2010 AACE Protocol for Production of Clinical Practice GuidelinesStep I: Evidence Rating

1 Meta-analysisofrandomizedcontrolledtrials(MRCT)1 Randomizedcontrolledtrial(RCT)2 Meta-analysisofnonrandomizedprospectiveorcase-controlledtrials(MNRCT)2 Nonrandomizedcontrolledtrial(NRCT)2 Prospectivecohortstudy(PCS)2 Retrospectivecase-controlstudy(RCCS)3 Cross-sectionalstudy(CSS)3 Surveillancestudy(registries,surveys,epidemiologicstudy)(SS)3 Consecutivecaseseries(CCS)3 Singlecasereports(SCR)4 Noevidence(theory,opinion,consensus,orreview)(NE)

Abbreviations:AACE=AmericanAssociationofClinicalEndocrinologists1=strongevidence;2=intermediateevidence;3=weakevidence;4=noevidence.AdaptedfromMechanicketal.Endocr Pract.2010.16:270-283.

2010 AACE Protocol for Production of Clinical Practice GuidelinesStep II: Evidence Analysis and Subjective Factors

Study design Data analysis Interpretation of resultsPremisecorrectness Intent-to-treat GeneralizabilityAllocationconcealment(randomization) Appropriatestatistics LogicalSelectionbias IncompletenessAppropriateblinding ValidityUsingsurrogateendpoints(especiallyin“first-in-its-class”intervention)Samplesize(betaerror)

NullhypothesisversusBayesianstatistics

Abbreviations:AACE=AmericanAssociationofClinicalEndocrinologistsAdaptedfromMechanicketal.Endocr Pract.2010.16:270-283.

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• High level of clarity and sufficient granular detail to facilitate implementation, and

• Expiration date after 3 years, during which time updating may be necessary, and after which time updating is considered

G4G-2014: CCs Specific indications for mandate. CCs must be relevant to clinical endocrine practice, fulfill a clear need based on patient safety, and implemented to primarily prevent errors of omission. Attributes. CCs will incorporate the following attributes:

• Comprehensive in nature for a given topic,• Identify objectives

o actionable steps that have adverse effects when skipped, and

o actionable steps that can optimize care,• Based only on strong recommendations (Grade A or B),• Unambiguous: using a high level of clarity to

facilitate implementation, • Single-page tear-out format, appropriate and sim-

ple use of fonts, colors, and logos for easy inter-pretation and use,

• Items in logical, time-sequenced, clusters corre-sponding to real-life scenarios or routines with natural breakso Preoperative versus postoperativeo Nursing intake, physician history/physical/

assessment/plan, and follow-up• Expiration date after 3 years, during which time

updating may be necessary, and after which time updating is considered

CONCLUSION

The practice of medicine relies heavily on rational thought, despite constant factual uncertainty and the bio-ethical challenges intrinsic to any human encounter. This process is complicated by scientific knowledge gaps. In a cognition-heavy medical subspecialty, such as endo-crinology, rational thinking should include creativity and intuition to manage these unknown or uncertain areas, but such thinking must still be based upon evidence- and expe-rience-based rules to achieve satisfactory levels of safety, effectiveness, and overall performance. Each of these 3 educational and clinical practice instruments (CPG, CA, and CC) serve to standardize and optimize care, facilitate accountability, and assure rationality in medical thinking (6). Their use will be increasingly incorporated within electronic health records and computerized medicine. Continued updating of these tools based on new medical information will improve and perpetuate their use. AACE continues to recognize the importance of these instruments

and will therefore revisit and update development and implementation strategies for clinical endocrinologists, including co-development efforts with other professional societies. In short, the AACE G4G program is a necessary process and enhances the AACE mission to optimize endo-crine care for our patients.

DISCLOSURE

Dr. Pauline Camacho reports that she has received advisory board honoraria from Intarcia Therapeutics, Inc. and Mission Pharmacal Company and research grant sup-port for her role as Principal Investigator from Amgen Inc. and Eli Lilly and Company. Dr. Alan J. Garber reports that he has received advi-sory board/consultant/speaker’s bureau honoraria from Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, and Vivus, Inc.; consultant/speaker’s bureau honoraria from Santarus, Inc.; advisory board honoraria from Halozyme Therapeutics, Inc.; and consultant hono-raria from Lexicon Pharmaceuticals, Inc. Dr. Jeffrey Garber reports that he does not have any relevant financial relationships with any commercial interests. Dr. Jeffrey I. Mechanick reports that he has received honoraria for lectures and program development by Abbott Nutrition. Dr. Mor Peleg reports that she does not have any rele-vant financial relationships with any commercial interests. Dr. Rachel Pessah-Pollack reports that she does not have any relevant financial relationships with any commer-cial interests. Dr. Steven M. Petak reports that he does not have any relevant financial relationships with any commercial interests. Dr. Vin Tangpricha reports that he has received hono-raria for his role as journal editor from Elsevier B.V. and grant support for his role as Principal Investigator from the Cystic Fibrosis Foundation. Dr. Dace Trence reports that she has received research grant support from Eli Lilly and Company and is a stock-holder of Medtronic, Inc. and sanofi-aventis U.S. LLC.

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